Comorbidities in Patients with Lichen Planopilaris: A Case-Control Study

Abstract

Introduction

Lichen planopilaris (LPP) is a lymphocyte-mediated type of scarring alopecia and considered to have autoimmune etiology. Studies about systemic comorbid conditions are limited. Our goal is to identify the prevalence of medical comorbidities in patients with LPP.

Methods

In a retrospective case-control study, the medical records of 208 LPP patients and 208 controls were reviewed for existing comorbidities such as thyroid diseases, cardiovascular disorders, hypertension, hyperlipidemia, and lupus erythematous.

Results

Hyperlipidemia was found in 41.8% of all patients with LPP and in 17.3% of controls (p value <0.001, OR = 4.167). Chances of hypertension and cardiovascular disorders were lower in the LPP group in comparison to controls (p value = 0.009). Thyroid disorders were more prevalent in LPP patients, but the difference was not statistically significant (p value = 0.277).

Conclusion

Our study further emphasizes that LPP patients should be screened for medical comorbidities, especially lipid profile abnormalities.

Introduction

Lichen planopilaris (LPP) is a rare lymphocyte-mediated inflammatory disease of the scalp which leads to scarring alopecia and is considered to have an autoimmune etiology [1, 2, 3]. Women are more commonly affected (60–90%) [3, 4]. The average age of the onset is 51.5 years, and usually, first symptoms appear at the age of 40–60 years [5].

The underling mechanism is unknown, but it is thought to be due to autoimmune reactions [1, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13]. Regarding that lichen planus (LP) is grouped as a T-cell-mediated autoimmune disease, it can be associated with other autoimmune diseases like systemic lupus erythematosus [6]. Up to now, a few studies have been done to show the comorbidities associated with LPP, either autoimmune diseases or nonautoimmune diseases [2, 6, 7, 12, 13, 14, 15, 16]. Recent studies have shown a relationship between LPP and thyroid disease, especially hypothyroidism. In addition, studies have focused on the relationship between LPP and diseases like diabetes, vitiligo, seborrheic dermatitis, hyperlipidemia, and cardiovascular disease [2, 6, 7, 9, 14, 17]. Medical comorbidities can influence decision-making to choose a treatment, so early recognition is important. Studies in this field are limited, and the results are contradictory. In this study, we decided to identify the prevalence of medical comorbidities in patients with LPP.

Materials and Methods

We performed a retrospective case-control study to evaluate the prevalence of comorbidities in patients diagnosed with LPP and compare it with the control group. We enrolled patients with histopathological confirmed LPP who were referred to the Razi hospital between 2013 and 2018. We did not include the frontal fibrosing alopecia (FFA) subtype in the study. The control group consisted of patients who were visited at the cosmetic clinic of the Razi hospital during different days of the week and randomly entered into our study and were sex-, age-, and body mass index-matched with the case group. Patients who had skin, mucosal, or nail lesions resembling LP and scarring alopecia or any skin diseases beside cosmetic problems were excluded from our control group. Information including age, sex, treatment history, family history of LPP, and duration of the disease from the beginning of scarring alopecia were obtained. History of medical illnesses such as thyroid diseases (abnormal thyroid-stimulating hormone, thyroxine, tri-iodothyronine level, or being under treatment for thyroid disorder), hypertension (systolic blood pressure over 120 mm Hg and diastolic blood pressure over 80 mm Hg or receiving antihypertensive drugs), lipid profile abnormality (total cholesterol level more than 200 mg/dL or triglyceride level more than 150 mg/dL or receiving lipid-lowering agents), cardiovascular disorders (confirmed ischemic heart disease, cerebrovascular disease, peripheral artery disease, and atherosclerosis), and systemic lupus erythematosus (based on American College of Rheumatology criteria) was assessed in both case and control groups. Severity of the disease was determined by an expert dermatologist based on the Lichen Planopilaris Activity Index (LPPAI) using the following formula: (symptoms + signs)/3 + 2.5 (pull test) + 1.5 (spread/2). The score ranges from 0 to 10. Symptoms (pruritus, pain, and burning) and signs (erythema, perifollicular erythema, and perifollicular scale) are recorded on a 4-point scale (0: absent, 1: mild, 2: moderate, and 3: severe). The anagen pull test (0: no anagen hair and 1: the presence of anagen hairs) and spreading of the condition (0: no spreading, 1: indeterminate, and 2: spreading) are also recorded [18]. Based on the calculated score, we categorized severity of disease into mild (0–3), moderate (4–7), and severe (8–10).

Statistical analysis was performed with SPSS 25 software, and 0.05 was considered as a significant level. For continuous and categorical variables, mean ± standard deviation and frequency (percentage) were reported. In order to assess the relationship between two categorical variables, the Chi-squared test and if needed, the Fisher exact test were used. For comparing the mean of two quantitative groups, the t test was used. The logistic regression model was used for multivariate analysis. This study was approved by the Research Ethics Committee of the Tehran University of Medical Sciences (IR.TUMS.MEDICINE.REC.1399.017).

Results

In this study, we included 416 patients (208 LPP patients and 208 controls). There were 299 women (76.9% in case group) in our study. The mean age of participants was 44.8 ± 15.2 years (47.24 ± 12.6 years in the case group and 42.39 ± 17.1 years in the control group). Four patients in the case group had a positive family history of LPP. The prevalence of comorbidities among LPP patients were as following: thyroid disorders (17.3%), hypertension (12.5%), lipid profile abnormalities (41.8%), and cardiovascular disease (5.3%).

The prevalence of thyroid disorders in the case group (36 patients) was more than that in the control group (28 patients), but the difference was not statistically significant (p value = 0.277). Among 36 patients with thyroid disorders in the case group, 33 patients were diagnosed as hypothyroidism, and remaining 3 patients had goiter, thyroid nodule, and papillary thyroid carcinoma. Comparison of hypothyroidism between case (33 patients) and control (27 patients) groups showed no significant relationship (p value = 0.402).

Hypertension was significantly lower in sex- and age-matched LPP patients (26 patients) compared to the control group (35 patients) (p value = 0.009). In addition, LPP patients had lower odds of cardiovascular disease in our study. We observed a significant difference in suffering from cardiovascular diseases between our case and control groups in sex- and age-matched groups (p value = 0.009). Besides, LPP patients had significantly more lipid profile diseases in sex- and age-matched groups (p value <0.001) (Fig. 1).

Fig. 1.

Prevalence of medical comorbidities in patients with LPP and the control group.

Other conditions in LPP patients were diabetes (12 patients), depression (6 patients), seborrheic dermatitis (6 patients), mucocutaneous LP (5 patients), basal-cell carcinoma (3 patients), breast fibroadenoma (2 patients), hyperprolactinemia (2 patients), allergic rhinitis, autoimmune thrombocytopenia, irritable bowel syndrome, hyperuricemia, asthma, rheumatoid arthritis, hepatitis C, cataract, glaucoma, and fatty liver (each 1 patient). Lupus erythematous was not detected in any of LPP patients, while 3 cases were diagnosed in the control group.

Mean age of LPP patients with thyroid disease was significantly more than patients with normal thyroid function tests (p value = 0.022), but there was not any significant difference in the control group. Hypertension, cardiovascular disorders, and hyperlipidemia were significantly more prevalent in older patients in both case and control groups. Thyroid disorders were more prevalent in female patients in both case and control groups, but there was no significant difference in sex of participants with hypertension, cardiovascular disorders, and hyperlipidemia. There was no significant relationship between severity and duration of LPP and comorbidities (Table 1).

Table 1.

Association of medical comorbidities with sex and age of participants and severity of disease

	Mean age, years		Sex				Severity of LPP
	control	case	control		case
			female	male	female	male	mild	moderate	severe
Thyroid disease
Yes	44.75	50.64	27	1	34	2	16	16	4
No	42.02	46.52
p value	0.02	0.43	<0.001		0.006		0.306
Cardiovascular disorders
Yes	56	59.09	17	5	10	1	6	4	1
No	40.78	46.57
p value	<0.001	<0.001	0.27		0.25		0.22
Hypertension
Yes	58.83	53.31	28	7	23	3	9	16	1
No	39.06	46,037
p value	<0.001	0.009	0.7		0.13		0.68
Hyperlipidemia
Yes	56.19	50.71	27	9	70	17	26	50	11
No	39.50	44.74
p value	<0.001	0.001	0.25		0.3		0.13

Discussion

LPP is a rare inflammatory lymphocyte-mediated disease of the scalp with autoimmune etiology. This disease leads to alopecia with scarring [1, 2, 3]. Previous studies showed association of LP with autoimmune disorders, hyperlipidemia, and hypothyroidism. Since LPP is a follicular variant of LP, the same associations can be found in these patients [14].

As previous studies which showed female predominance in LPP, in the current study 76.9% of patients were women [3, 4, 5]. We reported the prevalence of comorbidities among LPP patients as thyroid disorders (17.3%), cardiovascular disease (5.3%), hypertension (13.5%), and lipid profile disorders (41.8%). Hypertension and cardiovascular disease were significantly less, and lipid profile disorders were significantly more common in patients with LPP, whereas there was no significant difference in relation to thyroid disorders.

Results of a meta-analysis showed association of LP with dyslipidemia with higher levels of triglycerides, cholesterol, low-density lipoprotein, and lower level of high-density lipoprotein [19]. Dyslipidemia in LP patients may result from the effect of type 1 T-helper cells and cytokines such as tumor necrosis factor and interleukin 6 [20].

In study of Brankov et al. [14] with 334 LPP patients and 78 controls, the prevalence of hyperlipidemia was 38.6% in the case group and 52.6% in controls (p = 0.024), and thus, hyperlipidemia was negatively associated with LPP. In the study by Conic et al. [20], the rate of lipid-lowering drug prescription in the control group was more than that in LPP patients (26.8% vs. 18.7%), but the difference was not significant. However, a systematic review in 2020 demonstrated that there is no significant relationship between LPP and lipid profile abnormalities [17]. Various inflammatory skin conditions such as LP and psoriasis are associated with dyslipidemia probably due to pro-inflammatory cytokines [19]. Our study showed significant increase in dyslipidemia in LPP patients, and this observation can be explained by the same mechanism in other inflammatory disorders. The main reasons for the observed difference can be due to different sample sizes, duration of the disease, and definitions of hyperlipidemia in each study.

The prevalence of hypertension in a study of Fertig et al. [6] in case and control groups was 7.8% and 25.8%, respectively. The prevalence of hypertension was significantly lower in LPP patients (p value <0.01). Moreover, LPP patients were less prone to get cardiovascular diseases than controls [6, 15]. Our findings were in accordance with previous studies.

We observed no significant difference in thyroid disorders between our case and control groups, while in previous studies, the prevalence of thyroid disorders, especially hypothyroidism and Hashimoto's disease, was significantly higher in LPP patients [2, 14, 16]. However, other studies demonstrated that when FFA cases were excluded, and thyroid disorders were not more prevalent in LPP patients [6, 21]. Considering these findings, it seems that patients with the FFA subtype are more likely to have thyroid disease. Whether thyroid hormone receptors in the skin and related signaling can influence inflammatory status of skin in LPP patients and these pathways are different in LPP or FFA should be investigated in future studies [2].

We could not find any relationship between comorbidities and disease duration and severity. We propose that although LPP is a chronic inflammatory disorder, factors that contribute to severity and chronicity of disease are localized, but further studies are needed.

According to our study, cardiovascular disease and hypertension are less and dyslipidemia is more prevalent in patients with a confirmed diagnosis of LPP. However, more studies should be done to confirm the relationships. Screening for comorbidities and treatment of these disorders as soon as possible can be useful in increasing the life expectancy and quality of life of patients.

Statement of Ethics

This study protocol was reviewed and approved by Research Ethics Committee of the Tehran University of Medical Sciences, approval number IR.TUMS.MEDICINE.REC.1399.017. Written informed consent was obtained from participants (or their parent/legal guardian/next of kin) to participate in the study.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

The authors have received no external funding.

Author Contributions

All the authors meet the criteria for authorship. However, contribution details of each person are as follows: Maryam Nasimi: conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; and final approval of the version to be published. Gholamreza Garmaroudi: conception or design of the work and final approval of the version to be published. Maryam Ghiasi: conception or design of the work or the acquisition, analysis, or interpretation of data for the work. Vahideh Lajevardi: conception or design of the work or the acquisition, analysis, or interpretation of data for the work. Zahra Fooladi: the acquisition, analysis, or interpretation of data for the work and drafting the work. Mahgol Sadat Hasanzade Tabatabaee: drafting the work or revising it critically for important intellectual content. Mahshid Sadat Ansari: drafting the work or revising it critically for important intellectual content and final approval of the version to be published.

Data Availability Statement

The data that support the findings of this study are not publicly available due to privacy or ethical restrictions but are available on request from the corresponding author upon reasonable request.